Effects of volatile agents on neurophysiology in α-chloralose anesthetized rats

The mechanisms by which volatile anesthetics reduce neuronal activity in the mammalian central nervous system still need to be clarified^{1, 2}. Previous studies have shown that volatile anesthetics reduced neuronal activity in various parts of the CNS^{3, 4}. A mechanism that may contribute to neuronal depression concerns the effects on GABAA receptors ⁵ . The extent to which an increase in GABAA mediated synaptic inhibition contributes to the decreased neuronal firing must be explored further. In the present work, we have compared the effects of induction with volatile anesthetic agents halothane, isoflurane, and enflurane on neuronal activity and CBF of somatosensory cortical neurons in vivo for á-chloralose (40 mg/kg/hr) anesthetized rats, in the absence and presence of the competitive GABAA antagonist bicuculline (1 mg/kg). Sprague-Dawley rats were tracheotomized and artificially ventilated (70% N2O, 30% O2). During the animal preparation halothane (0.7%) / isoflurane (0.5%) / enflurane (0.5%) were used for induction. The Figure 1 shows changes in CBF and neuronal activity obtained during forepaw stimulation (2 mA, 3 Hz, 30 s) of rat in the somatosensory cortex (left panel) and during bicuculline induced seizure (right panel) under halothane/isoflurane or enflurane induction. With sensory stimulation there were increases in neuronal spiking frequency, local field potential, and CBF responses both when halothane and isoflurane were used for induction. In contrast enflurane-induction failed to produce very significant CBF responses to the same stimulation paradigm. To compare the effectiveness of the above-mentioned volatile induction agents in reducing neuronal activity and CBF, experiments were performed in presence of bicuculline. In the case of halothane and isoflurane induction, the patterns of the induced seizure were similar. On the contrary enflurane-induction showed a different pattern of seizure activity. Our results indicate that the above-mentioned volatile induction agents increased GABAA mediated synaptic inhibition and acted differently on GABAA receptors. In view of these findings we suggest that even mild exposure to volatile induction agents can have varied effects on GABAA receptors, which consequently affected stimulation-induced changes in neuronal activity and CBF responses.

Figure 1